Bacillus thuringiensis is a microbial insecticide that is widely used to control numerous insects, including agricultural pests; and, mosquitoes and blackflies, vectors of human diseases. The active components are the insecticidal crystal proteins or Cry toxins. These insecticidal proteins may be manipulated by genetic and protein engineering to alter and improve their activity. The overall goal of this project is to investigate in detail the binding of several Cry toxins to a known receptor and improve the insecticidal activity by improving the binding to the receptor. The specific aims are to identify the amino acid residues on the Cry toxins that interact with the receptor and to experimentally alter these residues to identify which substituted residues enhance binding and toxicity. This will be accomplished by the genetic technique of site-directed mutagenesis. The components on the receptor that are responsible for interaction with the toxin will also be determined biochemically. The proposed research employs a model system consisting of a cry toxins of known structure as a well characterized receptor. When the basic understanding of toxin-receptor interaction is obtained, this may used to improve Cry toxins against the mosquito.